The long-term goal of my research program is to elucidate the neural mechanisms that participate in the regulation of blood flow to rhythmically contracting human muscles. The specific goal of this application is to test the hypothesis that the reflex pressor response to ischemic exercise augments blood flow to the active muscles (i.e. the muscle chemoreflex hypothesis), and to determine if the effects on muscle blood flow of the reflex pressor responses generated by central command and the chemosensitive afferents are the same or different. This hypothesis will be studied experimentally in humans by manipulating perfusion pressure to rhythmically contracting forearm muscles and quantifying the effects of the altered perfusion pressure on blood flow to active muscles; and on the autonomic responses to the exercise. The following specific aims will be addressed: 1) Can increases in blood flow (above control values) to rhythmically contracting muscles blunt the pressor response to sympathetic activation normally associated with heavy rhythmic exercise? This will be studied by evaluating the effects of increased forearm blood flow on the autonomic responses to heavy rhythmic forearm exercise. 2) During the reflex pressor response, does increased sympathetic outflow to resistance vessels in the contracting muscles limit the ability of the augmented arterial pressure to improve blood flow to the active muscles? This will be studied by selective blockade of sympathetic vasoconstrictor fibers to contracting muscles during the reflex pressor response. 3) Do central command and muscle chemoreflex mediated increases in arterial pressure differ in their ability to increase blood flow to contracting muscles? This will be studied by comparing the effects of similar increases in blood pressure caused by partial neuromuscular blockade (increased central command) with that caused by post-exercise ischemia in a calf muscle (muscle chemoreflex activation) on blood flow to rhythmically contracting forearm muscles. These studies will provide highly focused, mechanistic information concerning reflex control of the circulation in humans.